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[Allergy to preservatives].

This study concerns 465 patients with dermatitis. The clinical history suggested allergy to cosmetics, drugs, industrial products or clothes. These patients were tested with 29 preservatives chosen among the most frequently employed or most sensitising products. Seven french clinics of Dermatology were involved in this study during one year. The patients' age varied between 2 years old and 80 years old. Positive reactions were seen mostly with formaldehyde (4.7 p. 100), Bronopol (4.7 p. 100), ammoniated mercury chloride (3.8 p. 100), benzoic acid (2.1 p. 100), sodium benzoate (1.9 p. 100), parabens (1.9 p. 100), dichlorophen (1.7 p. 100), chloracetamid (1.5 p. 100), benzyl benzoate (1.5 p. 100), Germall 115 (1.2 p. 100), butylhydroxyanisol (1 p. 100) and Dowicil (0.8 p. 100). The incidence of sensitivity to formaldehyde, Bronopol, ammoniated mercury chloride is too high; their use should decrease. Patients sensitive to benzoic acid, benzyl benzoate are not rare. Chloracetamid whose frequency of uses seems to be rather low is a very sensitising product. Parabens which are widely used were seldom found positive; nearly all cases are caused by topical medications.

Adolescent↗

Micromethod for measuring hexachlorophene in whole blood by gas-liquid chromatography.

We describe a micromethod for measuring hexachlorophene by use of gas-liquid chromatography with a 63Ni electron capture detector. The procedure requires 100 micronl of blood for extractions of hexachlorophene, and dichlorophene is added as an internal standard. CV is 3.4% over the concentration range of 500 to 1300 microng of hexachlorophene per liter of whole blood. This procedure permits repeated measurements of hexachlorophene in newborns who are being washed with soap containing hexachlorophene.

Chromatography, Gas↗

Effect of deworming medication on the microbial flora of the upper gastrointestinal tract of dogs.

Control cultures were taken at laporatomy of the stomach or stomach remnant, jejunum, and ileum of 26 adult dogs, 8 of which had had gastric surgery 1 yr earlier. Two wk after the control cultures were taken, 17 of the 26 dogs, including all 8 which had had prior surgery, were treated with anthelmintics, niclosamide, dichlorophene, methylbenzene, and arecoline hydrobromide. Two wk after the anthelmintic treatment, or 4 wk after the control cultures were taken, the 26 dogs were recultured. Samples of microbial flora were obtained by direct needle aspiration employing anaerobic precautions. These samples were processed both quantitatively and qualitatively using both anaerobic and aerobic technics. The specific sites cultured were the lower stomach or stomach remnant, proximal jejunum 15 cm distal to the ligament of Treitz, and distal ileum 45 cm proximal to the ileocecal valve. Bacteria isolated were predominately facultative aerobes. No fungi were isolated. Cultivation of spirochetes was not attempted. The results showed that there was no significant qualitative or quantitative alteration of microbial flora caused by the anthelmintic treatment.

Animals↗

Toxicological profile for o-benzyl-p-chlorophenol.

As part of a health-hazard survey on the health risk of hospital cleaning workers from exposure to Lyorthol, a hazard assessment of o-benzo-p-chlorophenol, one of the constituents of Lyorthol, has been prepared. In this paper, the physical and chemical characteristics, kinetics and effects of o-benzochlorophenol are described and discussed, and an overall, summarizing hazard evaluation is presented.

Administration, Oral↗

Chronic nephropathy and renal carcinogenicity of o-benzyl-p-chlorophenol in F344/N rats and B6C3F1 mice.

o-Benzyl-p-chlorophenol, an aryl halide biocide, was evaluated in male and female F344/N rats and B6C3F1 mice in a series of subchronic and 2-year toxicity and carcinogenicity studies. Kidney was the primary target of toxicity in the 13-week gavage studies in rats and mice, with increased nephropathy noted as low as 240 mg/kg in male rats. Considering the nephropathy to be doselimiting, the chronic (2-year) study was conducted at lower doses (male rats: 30, 60, or 120 mg/kg; female rats: 60, 120, or 240 mg/kg; male and female mice: 120, 240, or 480 mg/kg; in corn oil; n = 50/group). Survival and body weights of dosed rats were similar to controls in the 2-year study. Survival of high-dose male and female mice, and body weights of all dosed male and mid- and high-dose female mice, were lower than controls. The incidence and severity of nephropathy increased with dose and length of treatment in both rats and mice. There was an increased incidence of renal tubule adenomas or carcinomas in both the mid- and high-dose male mice. Despite similar evidence of nephropathy, however, there were no increased incidences of neoplasms in female mice or in male or female rats. This study suggests therefore that while nephrotoxicity may have been a necessary component, factors other than the marked nephrotoxicity of o-benzyl-p-chlorophenol were critical to the development of renal carcinogenesis induced in only male mice.

Adenoma↗

Determination of UV filters and antimicrobial agents in environmental water samples.

Although there is increasing concern about residues from personal care products entering the aquatic environment and their potential to accumulate to levels that pose a health threat to humans and wildlife, we still know little about the extent and magnitude of their presence in the aquatic environment. In this study we describe a procedure for isolation, and subsequent determination, of compounds commonly added to personal care products. The compounds of interest include UV filters with the commercial name Eusolex (homosalate, 4-methylbenzylidenecamphor, benzophenone-3, octocrylene, butylmethoxydibenzoylmethane, ethylhexyl methoxycinnamate) and two common anti-microbial agents, clorophene and triclosan. Water samples were filtered, acidified, and extracted by use of solid-phase extraction. Extracted compounds were then derivatised before analysis by gas chromatography-mass spectroscopy. By use of our method we obtained limits of detection of 13-266 ng L(-1) for UV filters, and 10-186 ng L(-1) for triclosan and clorophene. Recoveries were 82-98% for deionised water and 50-98% for natural water (seawater, pool water, lake water, and river water). Samples collected in Slovenia included seventeen recreational waters (seawater, pool water, lake water, and river water; August 2004) and four wastewaters (January 2005). The most abundant UV filter was benzophenone-3 (11-400 ng L(-1)). Of the two anti-microbial agents studied, trace amounts, only, of triclosan were present in the river Kolpa (68 ng L(-1)) and in an hospital effluent (122 ng L(-1)).

Anti-Infective Agents↗

Effect of o-benzyl-p-chlorophenol on drug-metabolizing enzymes in rats.

o-Benzyl-p-chlorophenol (BCP) is widely used as a broad spectrum disinfectant. Treatment of male Fischer 344 rats with BCP resulted in an increase in cytochrome P-450 content and an accompanying decrease in aryl hydrocarbon hydroxylase (AHH) activity in both liver and kidney microsomes. Several other drug-metabolizing enzymes were not affected by BCP treatment. However, in kidney, BCP induced NADPH-cytochrome c reductase and uridine diphosphate glucuronyl transferase activities and caused a small increase in total cytochrome P-450 content and glutathione concentration. The cytochrome P-450 isozymes induced by BCP were fractionated by high pressure liquid chromatography (HPLC). The HPLC profile following BCP treatment most closely resembled that seen after phenobarbital. Using an immunoblotting procedure and a radioimmunoassay, it was shown that the increase in cytochrome P-450 content in the liver after BCP treatment was, in part, due to an increase in the phenobarbital-inducible isozymes, P-450b + e. In the kidney, the increase in total cytochrome P-450 content after BCP exposure was not due to an increase in P-450b + e. The decrease in AHH activity appeared to be caused by noncompetitive inhibition of constitutive AHH activity by BCP. BCP also inhibited benzphetamine demethylation, although to a lesser extent. The failure to observe an increase in benzphetamine demethylase activity in vivo, despite the induction of P-450b, was probably due to the concomitant induction and inhibition of drug-metabolizing enzymes by BCP.

Animals↗

A growth inhibition test with sewage bacteria--results of an international ring test 1995.

A bacterial toxicity test method using the determination of growth inhibition of sewage bacteria within an incubation period of 6 hours will be standardized at ISO. A ring test was performed with 24 participants using 3.5-dichlorophenol and potassium cyanide as test substances. The analysis of the test results showed that the method is very accurate and appropriate for determining the bacterial toxicity of chemical compounds. Due to the results obtained 3.5-dichlorophenol was proposed as a reference substance.

Bacteria↗

Prechronic toxicity of o-benzyl-p-chlorophenol in rats and mice.

o-Benzyl-p-chlorophenol (BCP) is a major household and industrial germicide. Its prechronic toxicity was evaluated in male and female F344 rats and B6C3F1 mice. Treatment was by gavage in corn oil. BCP was slightly toxic after acute oral exposure, with high mortality at 4000 and 2000 mg/kg in rats and mice. Exposure to 12 oral doses of BCP at 1000, 500, 250, 125, 62.5, or 0 mg/kg body wt resulted in dose-related cecal dilatation and nephrosis in both rats and mice. Doses for the subchronic studies were based on the results of the 2-week studies. Ten animals were treated per dose per sex. Rats received 480, 240, 120, 60, 30, or 0 mg BCP/kg. Mice were treated with 1000, 800, 650, 500, or 0 mg BCP/kg. Animals were dosed 5 days per week for 13 weeks. Clinical signs related to dosing included urogenital staining in rats and rough/oily haircoats in mice. No effects on growth rate were seen in rats, but growth was retarded at the higher doses used in mice. Kidney weights increased in rats, and liver weights increased in mice. A decrease in thymus weight accompanied by a depletion in thymic lymphocytes (rats) or thymic necrosis (mice) occurred only in a high-dose animals. In both species, the kidney was the major target organ. In rats, there was an increase in incidence and severity of nephropathy and renal tubule regeneration. The lesions in mice primarily involved the renal cortex and included necrosis, casts, chronic inflammation, and regeneration of the renal tubules. No effects of BCP exposure in rats were seen in a broad spectrum of hematology or urinalysis parameters. Minor decreases in blood urea nitrogen, creatinine, and alanine amino transferase were detected in male and female rats. There were no biologically significant neurobehavioral effects in rats or immunotoxic effects in mice due to exposure to BCP. Thus, the kidney is the major target organ for BCP.

Animals↗

Ecotoxicological evaluation of the biocidal agents sodium o-phenylphenol, sodium o-benzyl-p-chlorophenol, and sodium p-tertiary amylphenol.

The ecotoxicological effects of three biocidal agents frequently employed as active ingredients in phenolic-based disinfectants were evaluated using a test battery comprising of organisms representing three aquatic trophic levels. Phenolic-based disinfectants are commonly used by mushroom growers to disinfect spent mushroom compost. In general, the most sensitive assay used in this study was the Microtox test. In the case of the fish lethality assay, sodium o-benzyl-p-chlorophenol was found to be slightly more sensitive than the bacterial test system. The freshwater alga and invertebrate tests were also among the most sensitive test species employed. The active ingredient, sodium o-benzyl-p-chlorophenol (with the exception of the Microtox assay), was the most toxic chemical tested on each species. The majority of ecotoxicity data obtained in this research has not been previously reported and may therefore assist in the management and planning decisions regarding the application of pesticides and utilisation of SMC.

Agaricales↗

In vitro cytotoxicity assessment of the biocidal agents sodium o-phenylphenol, sodium o-benzyl-p-chlorophenol, and sodium p-tertiary amylphenol using established fish cell lines.

The cytotoxicity of three biocidal agents frequently employed as active ingredients in phenolic-based disinfectants, were evaluated in three established fish cell lines (EPC, CHSE and RTG-2). Cell viability was assessed using two fluorescent indicator dyes, Alamar Blue for metabolism and neutral red for lysosomal activity. Total protein content was also quantified as a measure of cell detachment. In order to evaluate the sensitivity of the cell cultures, the results obtained were compared with toxicity data obtained from a previous study with the same three compounds and the in vivo lethality test with rainbow trout. Results from this study established that each of the three cell lines ranked the tested chemicals in the same order of toxicity as the in vivo test; however, the cell cultures were found to be an order of magnitude less sensitive than whole fish studies with the same compounds. The chemical sodium o-benzyl-p-chlorophenol was consistently ranked the most toxic of the tested compounds with each cell line and the endpoints employed. The rank order of toxicity was always sodium o-benzyl-p-chlorophenol > sodium p-tertiary amylphenol > sodium o-phenylphenol. The EPC cells were found to be the most sensitive cell line tested based on Alamar Blue IC(50) data, and the Alamar Blue assay was consistently found to be the most sensitive endpoint of the three cytotoxicity assays employed.

Animals↗

Identification of estrogenic compounds in fish bile using bioassay-directed fractionation.

Conjugates of estrogenic chemicals, endogenous as well as xenobiotic, are mainly excreted via bile into the intestine. Therefore, measurement of estrogenic activity in bile yields useful information about an organism's internal exposure to (xeno-)estrogens. Although previous studies in The Netherlands have reported estrogenic activity in male fish bile, the contribution of natural hormones and xenobiotic substances to this activity is unknown. To identify compounds responsible for estrogenic activity in fish bile, we developed a bioassay-directed fractionation method for estrogenic chemicals. In this approach, the in vitro reporter gene assay ER-CALUX (Estrogen Responsive Chemical Activated Luciferase Gene Expression) was used to assess estrogenic activity in deconjugated bile samples and to direct RP-HPLC fractionation and chemical analysis (by GC-MS) of estrogenic compounds. The method was applied to bile from male breams (Abramis brama) collected at three locations in The Netherlands. At one of these locations, the River Dommel, extremely high levels of plasma vitellogenin and a high incidence of intersex gonads in these male breams have previously been observed, indicating the exposure to estrogens. In this study, the natural hormones 17beta-estradiol, estrone, and estriol accounted for the majority of estrogenic activity in male bream bile. At the River Dommel, the synthetic contraceptive pill component ethynylestradiol was found in effective concentrations as well. The detected natural and synthetic hormones may be responsible forthe estrogenic effects observed in wild bream from this location. Furthermore, a large number of xenobiotic chemicals was detected at relatively high levels in bile, including triclosan, chloroxylenol, and clorophene. Although chloroxylenol was shown for the first time to be weakly estrogenic, these compounds did not contribute significantly to the estrogenic activity observed.

Animals↗

Effects of chlorinated bisphenols on torula yeast glucose-6-phosphate dehydrogenase.

Chlorinated bisphenol antibacterial and antifungal agents are potent inhibitors of torula yeast glucose-6-phosphate dehydrogenase (G6PD). Several compounds were tested, including hexachlorophene [HCP; 2,2'-methylenebis(3,4,6-trichlorophenol)]; 2,2'-oxybis(tetrachlorophenol); 2',4-dihydroxy-2,3,3',5,5',6-hexachlorodiphenylmethane; 2,2'-methylenebis(3,4-dichlorophenol) (3,4-TCP); bithionol [2,2'-thiobis(4,6-dichlorophenol)]; 2,2'-methylenebis(3,5-dichlorophenol); 2,2'-dihydroxy-3,3',5,6,6'-pentachlorodiphenylmethane; 2,2'-methylenebis(4-chlorophenol) (DCP); 2,2'-methylenebis(4,6-dichlorophenol); and the related uncoupler 2,4-dinitrophenol. The relative inhibitory activity of the chlorinated bisphenols tended to increase with degree of chlorination of the aromatic rings. the concentrations of the bisphenols that caused 50% inhibition ranged from 2.5 micrometers for 2,2'-oxybis(tetrachlorophenol) to 40 micrometers for 2,2'-methylenebis(4,6-dichlorophenol) under comparable assay conditions. More detailed kinetic analysis showed that, as with HCP, the inhibition of G6PD by 3,4-TCP and DCP followed noncompetitive kinetics. Calculations from the kinetic data gave apparent inhibition constant (Ki) values for 3,4-TCP of 267 micrometers with G6P and 308 micrometers with NADP, and for DCP of 697 micrometers with both G6P and NADP.

Anti-Infective Agents↗